The purpose of this study was to compare monotherapy to combination nucleocide analogue therapy in HIV+ persons without AIDS and with CD4 counts between 200 and 500/mm3. Patients received ZDV alone, ZDV + ddI, ZDV + ddC, or ddI alone. A decline in CD4 cell numbers to less than 50% of baseline values were used as a landmark for evaluation in addition to clinical progression. ACTG 175 closed with 2,467 eligible subjects being randomized to receive ZDV alone, ddI alone, ZDV/ddI or ZDV/ddC. In attempting to frame a practical synthesis from the results, ZDV naive and experienced subjects should be considered separately. For ZDV naive patients, initiation of treatment with ddI, ZDV/ddI, or ZDV/ddC has been shown to be clearly superior to ZDV monotherapy in delaying the development of a study endpoint (a 50% decline in CD4 counts, AIDS or death), and there were similar trends for clinical endpoints. For ZDV experienced patients, ddI and ZDV/ddI were found to be superior to continued ZDV monotherapy, and these comparisons also demonstrated a survival benefit. The results of ACTG 175 together with results from earlier studies validate the position that antiretroviral therapy is of benefit to asymptomatic patients with CD4 counts under 500 and, for the first time, show that an improvement in survival can be demonstrated in an intermediate disease stage population. This study also reconfirms the importance of careful planning in using antiretroviral regimens, as prior antiretroviral experience may substantially influence efficacy, as was seen for the combination of ZDV/ddC in this study. Subjects who were enrolled in ACTG 175 and were originally randomized to combination nucleoside analog therapy, or who were crossed over to combination therapy during the course of the trial and continued to take the same combination therapy, were entered in ACTG 303, "An influence of risk status for disease progression on the response to antiretroviral interventions". ACTG 175 subjects who remained on their original ZDV or ddI monotherapy assignment through the completion of ACTG 175 and during any additional interval were enrolled in ACTG 302, "Virologic responses to new nucleoside regimens after prolonged ZDV or ddI monotherapy".